Clinical activity in general practice prior to sarcoma diagnosis: Australian cohort study.

Background Increased time-to-diagnosis in sarcoma is associated with poor prognosis and patient outcomes. Research is needed to identify if opportunities to expedite the diagnosis of sarcoma in general practice (GP) exist. Aim To examine pre-diagnostic GP clinical activity prior to sarcoma diagnosis. Design and Setting An Australian retrospective cohort study using hospital registry data (Australian Comprehensive Cancer Outcomes and Research Database) linked to two primary care datasets (Patron and MedicineInsight). Method The frequency of GP healthcare utilisation events (GP attendances, prescriptions, blood test and imaging requests) were compared in 377 soft tissue sarcoma (STS) and 64 bone sarcoma (BS) patients in the year pre-diagnosis. Poisson regression models were used to calculate monthly incidence rates and rate ratios (IRR) for the 24 months pre-diagnosis and estimate inflection points for when healthcare use starts to increase from baseline. Results In the six months pre-diagnosis sarcoma patients had a median of 3-4 GP attendances, a third had a GP imaging request (33% BS and 36% STS), and one in five had multiple imaging requests (19% BS and 21% STS). GP imaging requests progressively increased up to 8-fold from 6 months prior to sarcoma diagnosis (IRR 8.43 95%CI 3.92-18.15, p<0.001) and GP attendances increased from 3 months pre-diagnosis. Conclusion Sarcoma patients have increased GP clinical activity from 6 months pre-diagnosis, indicating a diagnostic window where potential opportunities exist for earlier diagnosis. Interventions to help identify patients and promote appropriate use of imaging and direct specialist centre referrals could improve earlier diagnosis and patient outcomes.

Guideline concordance for timely chest imaging after new presentations of dyspnoea or haemoptysis in primary care: a retrospective cohort study.

BACKGROUND: Guidelines recommend urgent chest X-ray for newly presenting dyspnoea or haemoptysis but there is little evidence about their implementation. METHODS: We analysed linked primary care and hospital imaging data for patients aged 30+ years newly presenting with dyspnoea or haemoptysis in primary care during April 2012 to March 2017. We examined guideline-concordant management, defined as General Practitioner-ordered chest X-ray/CT carried out within 2 weeks of symptomatic presentation, and variation by sociodemographic characteristic and relevant medical history using logistic regression. Additionally, among patients diagnosed with cancer we described time to diagnosis, diagnostic route and stage at diagnosis by guideline-concordant status. RESULTS: In total, 22 560/162 161 (13.9%) patients with dyspnoea and 4022/8120 (49.5%) patients with haemoptysis received guideline-concordant imaging within the recommended 2-week period. Patients with recent chest imaging pre-presentation were much less likely to receive imaging (adjusted OR 0.16, 95% CI 0.14-0.18 for dyspnoea, and adjusted OR 0.09, 95% CI 0.06-0.11 for haemoptysis). History of chronic obstructive pulmonary disease/asthma was also associated with lower odds of guideline concordance (dyspnoea: OR 0.234, 95% CI 0.225-0.242 and haemoptysis: 0.88, 0.79-0.97). Guideline-concordant imaging was lower among dyspnoea presenters with prior heart failure; current or ex-smokers; and those in more socioeconomically disadvantaged groups.The likelihood of lung cancer diagnosis within 12 months was greater among the guideline-concordant imaging group (dyspnoea: 1.1% vs 0.6%; haemoptysis: 3.5% vs 2.7%). CONCLUSION: The likelihood of receiving urgent imaging concords with the risk of subsequent cancer diagnosis. Nevertheless, large proportions of dyspnoea and haemoptysis presenters do not receive prompt chest imaging despite being eligible, indicating opportunities for earlier lung cancer diagnosis.

Pre-diagnostic prescribing patterns in dyspnoea patients with as-yet-undiagnosed lung cancer: A longitudinal study of linked primary care and cancer registry data.

INTRODUCTION: Patients with as-yet undiagnosed lung cancer (LC) can present to primary care with non-specific symptoms such as dyspnoea, often in the context of pre-existing chronic obstructive pulmonary disease (COPD). Related medication prescriptions pre-diagnosis might represent opportunities for earlier diagnosis, but UK evidence is limited. Consequently, we explored prescribing patterns of relevant medications in patients who presented with dyspnoea in primary care and were subsequently diagnosed with LC. METHOD: Linked primary care (Clinical Practice Research Datalink) and National Cancer Registry data were used to identify 5434 patients with incident LC within a year of a dyspnoea presentation in primary care between 2006 and 2016. Primary care prescriptions relevant to dyspnoea management were examined: antibiotics, inhaled medications, oral steroids, and opioid analgesics. Poisson regression models estimated monthly prescribing rates during the year pre-diagnosis. Variation by COPD status (52 % pre-existing, 36 % COPD-free, 12 % new-onset) was examined. Inflection points were identified indicating when prescribing rates changed from the background rate. RESULTS: 63 % of patients received 1 or more relevant prescriptions 1-12 months pre-diagnosis. Pre-existing COPD patients were most prescribed inhaled medications. COPD-free and new-onset COPD patients were most prescribed antibiotics. Most patients received 2 or more relevant prescriptions. Monthly prescribing rates of all medications increased towards time of diagnosis in all patient groups and were highest in pre-existing COPD patients. Increases in prescribing activity were observed earliest in pre-existing COPD patients 5 months pre-diagnosis for inhaled medications, antibiotics, and steroids, CONCLUSION: Results indicate that a diagnostic window of appreciable length exists for potential earlier LC diagnosis in some patients. Lung cancer diagnosis may be delayed if early symptoms are misattributed to COPD or other benign conditions.

The Role of Type 2 Diabetes in Patient Symptom Attribution, Help-Seeking, and Attitudes to Investigations for Colorectal Cancer Symptoms: An Online Vignette Study.

OBJECTIVES: Type 2 diabetes is associated with a higher risk of colorectal cancer (CRC) and advanced-stage cancer diagnosis. To help diagnose cancer earlier, this study aimed at examining whether diabetes might influence patient symptom attribution, help-seeking, and willingness to undergo investigations for possible CRC symptoms. METHODS: A total of 1307 adults (340 with and 967 without diabetes) completed an online vignette survey. Participants were presented with vignettes describing new-onset red-flag CRC symptoms (rectal bleeding or a change in bowel habits), with or without additional symptoms of diabetic neuropathy. Following the vignettes, participants were asked questions on symptom attribution, intended help-seeking, and attitudes to investigations. RESULTS: Diabetes was associated with greater than two-fold higher odds of attributing changes in bowel habits to medications (OR = 2.48; 95% Cl 1.32-4.66) and of prioritising diabetes-related symptoms over the change in bowel habits during medical encounters. Cancer was rarely mentioned as a possible explanation for the change in bowel habits, especially among diabetic participants (10% among diabetics versus 16% in nondiabetics; OR = 0.55; 95% CI 0.36-0.85). Among patients with diabetes, those not attending annual check-ups were less likely to seek help for red-flag cancer symptoms (OR = 0.23; 95% Cl 0.10-0.50). CONCLUSIONS: Awareness of possible cancer symptoms was low overall. Patients with diabetes could benefit from targeted awareness campaigns emphasising the importance of discussing new symptoms such as changes in bowel habits with their doctor. Specific attention is warranted for individuals not regularly attending healthcare despite their chronic morbidity.

Steroid prescribing in primary care increases prior to Hodgkin lymphoma diagnosis: A UK nationwide case-control study.

BACKGROUND: Steroid use is associated with increased risk of Hodgkin lymphoma (HL). However, allergic symptoms commonly treated with steroids are also presenting features of HL in some patients, thereby introducing protopathic bias in estimates of aetiological associations. It is therefore important to examine steroid prescribing patterns pre-diagnosis to understand timing of associations and when healthcare use increases before cancer diagnosis to inform future epidemiological study design. METHODS: We analysed steroid prescribing in 1232 HL patients and 7392 matched controls using primary care electronic health records (Clinical Practice Research Datalink (CPRD), 1987-2016). Using Poisson regression, we calculated monthly steroid prescribing rates for the 24-months preceding HL diagnosis, identifying the inflection point when they start to increase from baseline in cases, comparing rates with synchronous controls, and stratifying by route-of-administration and allergic disease status. RESULTS: 46 % of HL patients had a steroid prescription in the 24-months preceding diagnosis compared to 26 % of controls (OR 2.55, 95 %CI 2.25-2.89, p < 0.001). Odds of underlying HL were greatest in patients receiving multiple steroid prescriptions, oral steroids and in patients with a new allergic disease diagnosis. Among HL patients, steroid prescribing rates increased progressively from 7-months pre-diagnosis, doubling from 52 to 111 prescriptions/1000 patients/month. CONCLUSION: Steroid prescribing increases during periods leading up to HL diagnosis, suggesting steroid-treated symptoms may be early presenting features of HL. A diagnostic window of appreciable length exists for potential earlier HL diagnosis in some patients; this 7-month 'lag-period' pre-diagnosis should be excluded in studies examining aetiological associations between steroids and HL.

Inflammatory marker testing in primary care in the year before Hodgkin lymphoma diagnosis: a UK population-based case-control study in patients aged ≤50 years.

BACKGROUND: Proinflammatory conditions are associated with increased risk of Hodgkin lymphoma, although the neoplastic process per se often induces an inflammatory response. AIM: To examine pre-diagnostic inflammatory marker test use to identify changes that may define a 'diagnostic window' for potential earlier diagnosis. DESIGN AND SETTING: This was a matched case-control study in UK primary care using Clinical Practice Research Datalink data (2002-2016). METHOD: Primary care inflammatory marker test use and related findings were analysed in 839 Hodgkin lymphoma patients and 5035 controls in the year pre-diagnosis. Poisson regression models were used to calculate monthly testing rates to examine changes over time in test use. Longitudinal trends in test results and the presence/absence of 'red-flag' symptoms were examined. RESULTS: In patients with Hodgkin lymphoma, 70.8% (594/839) had an inflammatory marker test in the year pre-diagnosis versus 16.2% (816/5035) of controls (odds ratio 13.7, 95% CI = 11.4 to 16.5, P<0.001). The rate of inflammatory marker testing and mean levels of certain inflammatory marker results increased progressively during the year pre-diagnosis in Hodgkin lymphoma patients while remaining stable in controls. Among patients with Hodgkin lymphoma with a pre-diagnostic test, two-thirds (69.5%, 413/594) had an abnormal result and, among these, 42.6% (176/413) had no other 'red-flag' presenting symptom/sign. CONCLUSION: Increases in inflammatory marker requests and abnormal results occur in many patients with Hodgkin lymphoma several months pre-diagnosis, suggesting this period should be excluded in aetiological studies examining inflammation in Hodgkin lymphoma development, and that a diagnostic time window of appreciable length exists in many patients with Hodgkin lymphoma, many of whom have no other red-flag features.

Impact of a case-management intervention for reducing emergency attendance on primary care: randomised control trial.

BACKGROUND: The impact on primary care workload of case-management interventions to reduce emergency department (ED) attendances is unknown. AIM: To examine the impact of a telephone-based case-management intervention targeting people with high ED attendance on primary care use. DESIGN AND SETTING: A single-site data extract from a larger randomised control trial, using the patient-level data from primary care electronic health records (2015-2020), was undertaken. METHOD: A total of 363 patients at high risk of ED usage were randomised to receive a 6-month case-management intervention (253 patients) or standard care (110 patients). Poisson regression models were used to calculate monthly rates of primary care use over time for the 2 years post-randomisation, comparing both arms. Usage was subclassified into face-to-face, telephone, letter, and community and secondary care referrals, stratified by patient demographics. RESULTS: No significant difference was found in the mean annual rate of primary care events between the intervention and control arms (P = 0.70). Secondary care referrals saw a 26% reduction in the mean annual referral rate (incident rate ratio [IRR] 0.74, 95% confidence interval [CI] = 0.64 to 0.86, P<0.001) and letters sent increased by 6% in the intervention arm compared with the control arm (IRR 1.06, 95% CI = 1.01 to 1.11, P = 0.01). In the case-managed arm, in patients aged ≥80 years there was a 33% increase in primary care usage (IRR 1.33, 95% CI = 1.28 to 1.40, P<0.001); with a corresponding 10% decrease in patients aged <80 years when compared with controls (IRR 0.90, 95% CI = 0.87 to 0.92, P<0.001). CONCLUSION: A targeted case-management intervention to reduce ED attendances did not increase overall primary care use. Redistribution of usage is seen among some patient groups, particularly older people, which may have important implications for primary healthcare planning.

Risk of cancer following primary care presentation with fatigue: a population-based cohort study of a quarter of a million patients.

BACKGROUND: The management of adults presenting with fatigue presents a diagnostic challenge, particularly regarding possible underlying cancer. METHODS: Using electronic health records, we examined cancer risk in patients presenting to primary care with new-onset fatigue in England during 2007-2013, compared to general population estimates. We examined variation by age, sex, deprivation, and time following presentation. FINDINGS: Of 250,606 patients presenting with fatigue, 12-month cancer risk exceeded 3% in men aged 65 and over and women aged 80 and over, and 6% in men aged 80 and over. Nearly half (47%) of cancers were diagnosed within 3 months from first fatigue presentation. Site-specific cancer risk was higher than the general population for most cancers studied, with greatest relative increases for leukaemia, pancreatic and brain cancers. CONCLUSIONS: In older patients, new-onset fatigue is associated with cancer risk exceeding current thresholds for urgent specialist referral. Future research should consider how risk is modified by the presence or absence of other signs and symptoms. Excess cancer risk wanes rapidly after 3 months, which could inform the duration of a 'safety-netting' period. Fatigue presentation is not strongly predictive of any single cancer, although certain cancers are over-represented; this knowledge can help prioritise diagnostic strategies.

Does changing healthcare use signal opportunities for earlier detection of cancer? A review of studies using information from electronic patient records.

BACKGROUND: It has been proposed that changes in healthcare use before cancer diagnosis could signal opportunities for quicker detection, but systematic appreciation of such evidence is lacking. We reviewed studies examining pre-diagnostic changes in healthcare utilisation (e.g. rates of GP or hospital consultations, prescriptions or diagnostic tests) among patients subsequently diagnosed with cancer. METHODS: We identified studies through Pubmed searches complemented by expert elicitation. We extracted information on the earliest time point when diagnosis could have been possible for at least some cancers, together with variation in the length of such 'diagnostic windows' by tumour and patient characteristics. RESULTS: Across twenty-eight studies, changes in healthcare use were observable at least six months pre-diagnosis for many common cancers, and potentially even earlier for colorectal cancer, multiple myeloma and brain tumours. Early changes were also identified for brain and colon cancer sub-sites. CONCLUSION: Changing healthcare utilisation patterns before diagnosis indicate that future improvements in diagnostic technologies or services could help to shorten diagnostic intervals for cancer. There is greatest potential for quicker diagnosis for certain cancer types and patient groups, which can inform priorities for the development of decision support tools.

Predictive values for different cancers and inflammatory bowel disease of 6 common abdominal symptoms among more than 1.9 million primary care patients in the UK: A cohort study.

BACKGROUND: The diagnostic assessment of abdominal symptoms in primary care presents a challenge. Evidence is needed about the positive predictive values (PPVs) of abdominal symptoms for different cancers and inflammatory bowel disease (IBD). METHODS AND FINDINGS: Using data from The Health Improvement Network (THIN) in the United Kingdom (2000-2017), we estimated the PPVs for diagnosis of (i) cancer (overall and for different cancer sites); (ii) IBD; and (iii) either cancer or IBD in the year post-consultation with each of 6 abdominal symptoms: dysphagia (n = 86,193 patients), abdominal bloating/distension (n = 100,856), change in bowel habit (n = 106,715), rectal bleeding (n = 235,094), dyspepsia (n = 517,326), and abdominal pain (n = 890,490). The median age ranged from 54 (abdominal pain) to 63 years (dysphagia and change in bowel habit); the ratio of women/men ranged from 50%:50% (rectal bleeding) to 73%:27% (abdominal bloating/distension). Across all studied symptoms, the risk of diagnosis of cancer and the risk of diagnosis of IBD were of similar magnitude, particularly in women, and younger men. Estimated PPVs were greatest for change in bowel habit in men (4.64% cancer and 2.82% IBD) and for rectal bleeding in women (2.39% cancer and 2.57% IBD) and lowest for dyspepsia (for cancer: 1.41% men and 1.03% women; for IBD: 0.89% men and 1.00% women). Considering PPVs for specific cancers, change in bowel habit and rectal bleeding had the highest PPVs for colon and rectal cancer; dysphagia for esophageal cancer; and abdominal bloating/distension (in women) for ovarian cancer. The highest PPVs of abdominal pain (either sex) and abdominal bloating/distension (men only) were for non-abdominal cancer sites. For the composite outcome of diagnosis of either cancer or IBD, PPVs of rectal bleeding exceeded the National Institute of Health and Care Excellence (NICE)-recommended specialist referral threshold of 3% in all age-sex strata, as did PPVs of abdominal pain, change in bowel habit, and dyspepsia, in those aged 60 years and over. Study limitations include reliance on accuracy and completeness of coding of symptoms and disease outcomes. CONCLUSIONS: Based on evidence from more than 1.9 million patients presenting in primary care, the findings provide estimated PPVs that could be used to guide specialist referral decisions, considering the PPVs of common abdominal symptoms for cancer alongside that for IBD and their composite outcome (cancer or IBD), taking into account the variable PPVs of different abdominal symptoms for different cancers sites. Jointly assessing the risk of cancer or IBD can better support decision-making and prompt diagnosis of both conditions, optimising specialist referrals or investigations, particularly in women.

General Practice in the Time of COVID-19: A Mixed-Methods Service Evaluation of a Primary Care COVID-19 Service.

Primary care coronavirus disease 2019 (COVID-19) clinics were rapidly introduced across the UK to review potentially infectious patients. Evaluation of these services is needed to guide future implementation. This mixed-methods study evaluates patient demographics, clinical presentation, co-morbidities, service usage, and outcomes for the Islington COVID-19 service (London, UK) and from April to May 2020 and thematically analyses survey responses from 29 service clinicians and 41 GP referrers on their service experience. Of the 237 patients booked into the service, a significant number of referrals (n = 91; 38.6%) were made after the presumed infectious period of 14 days. Almost half of all adult referrals (49%) were dealt with remotely (via telephone/video consultation +/- remote oxygen saturation monitoring). The service was perceived to provide a safe way to see patients; it developed local expertise, learning, and empowerment; and it was a positive teamworking experience. These findings suggest that the management of many patients with COVID-19 symptoms is possible in routine general practice with minimal risk through the implementation of remote consultation methods and in patients who present after the post-infectious period. Additionally, the use of remote saturation monitoring and local GP COVID-19 "experts" can support practices to manage COVID-19 patients. Future primary care COVID-19 services should act as empowerment tools to assist GPs to safely manage their own patients and provide support for GPs in this process.

Opportunities to reduce antibiotic prescribing for patients with COPD in primary care: a cohort study using electronic health records from the Clinical Practice Research Datalink (CPRD).

BACKGROUND: In primary care there is uncertainty about which patients with acute exacerbations of COPD (AECOPD) benefit from antibiotics. OBJECTIVES: To identify which types of COPD patients get the most antibiotics in primary care to support targeted antibiotic stewardship. METHODS: Observational study of COPD patients using a large English primary care database with 12 month follow-up. We estimated the incidence of and risk factors for antibiotic prescribing relative to the number of AECOPD during follow-up, considering COPD severity, smoking, obesity and comorbidity. RESULTS: From 157 practices, 19594 patients were diagnosed with COPD, representing 2.6% of patients and 11.5% of all prescribed antibiotics. Eight hundred and thirty-three (4.5%) patients with severe COPD and frequent AECOPD were prescribed six to nine prescriptions per year and accounted for 13.0% of antibiotics. Individuals with mild to moderate COPD and zero or one AECOPD received one to three prescriptions per year but accounted for 42.5% of all prescriptions. In addition to COPD severity, asthma, chronic heart disease, diabetes, heart failure and influenza vaccination were independently associated with increased antibiotic use. CONCLUSIONS: Patients with severe COPD have the highest rates of antibiotic prescribing but most antibiotics are prescribed for patients with mild to moderate COPD. Antibiotic stewardship should focus on the dual goals of safely reducing the volume of prescribing in patients with mild to moderate COPD, and optimizing prescribing in patients with severe disease who are at significant risk of drug resistance.

Allergic disease, corticosteroid use, and risk of Hodgkin lymphoma: A United Kingdom nationwide case-control study.

BACKGROUND: Immunodeficiency syndromes (acquired/congenital/iatrogenic) are known to increase Hodgkin lymphoma (HL) risk, but the effects of allergic immune dysregulation and corticosteroids are poorly understood. OBJECTIVE: We sought to assess the risk of HL associated with allergic disease (asthma, eczema, and allergic rhinitis) and corticosteroid use. METHODS: We conducted a case-control study using the United Kingdom Clinical Practice Research Datalink (CPRD) linked to hospital data. Multivariable logistic regression investigated associations between allergic diseases and HL after adjusting for established risk factors. Potential confounding or effect modification by steroid treatment were examined. RESULTS: One thousand two hundred thirty-six patients with HL were matched to 7416 control subjects. Immunosuppression was associated with 6-fold greater odds of HL (adjusted odds ratio [aOR], 6.18; 95% CI, 3.04-12.57), with minimal change after adjusting for steroids. Any prior allergic disease or eczema alone was associated with 1.4-fold increased odds of HL (aOR, 1.41 [95% CI, 1.24-1.60] and 1.41 [95% CI, 1.20-1.65], respectively). These associations decreased but remained significant after adjustment for steroids (aOR, 1.25 [95% CI, 1.09-1.43] and 1.27 [95% CI, 1.08-1.49], respectively). There was no effect modification by steroid use. Previous steroid treatment was associated with 1.4-fold greater HL odds (aOR, 1.38; 95% CI, 1.20-1.59). CONCLUSIONS: In addition to established risk factors (immunosuppression and infectious mononucleosis), allergic disease and eczema are risk factors for HL. This association is only partially explained by steroids, which are associated with increased HL risk. These findings add to the growing evidence that immune system malfunction after allergic disease or immunosuppression is central to HL development.

Socioeconomic deprivation and regional variation in Hodgkin's lymphoma incidence in the UK: a population-based cohort study of 10 million individuals.

OBJECTIVES: Hodgkin's lymphoma (HL) is the the most common cancer in teenagers and young adults. This nationwide study conducted over a 25-year period in the UK investigates variation in HL incidence by age, sex, region and deprivation to identify trends and high-risk populations for HL development. DESIGN: Population-based cohort study. SETTING: Clinical Practice Research Datalink (CPRD) electronic primary care records linked to Hospital Episode Statistics and Index of Multiple Deprivation data were used. PARTICIPANTS: Data on 10 million individuals in the UK from 1992 to 2016 were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: Poisson models were used to explore differences in HL incidence by age, sex, region and deprivation. Age-specific HL incidence rates by sex and directly age-standardised incidence rates by region and deprivation group were calculated. RESULTS: A total of 2402 new cases of HL were identified over 78 569 436 person-years. There was significant variation in HL incidence by deprivation group. Individuals living in the most affluent areas had HL incidence 60% higher than those living in the most deprived (incidence rate ratios (IRR) 1.60, 95% CI 1.40 to 1.83), with strong evidence of a marked linear trend towards increasing HL incidence with decreasing deprivation (p=<0.001). There was significant regional variation in HL incidence across the UK, which persisted after adjusting for age, sex and deprivation (IRR 0.80-1.42, p=<0.001). CONCLUSIONS: This study identified high-risk regions for HL development in the UK and observed a trend towards higher incidence of HL in individuals living in less deprived areas. Consistent with findings from other immune-mediated diseases, this study supports the hypothesis that an affluent childhood environment may predispose to development of immune-related neoplasms, potentially through fewer immune challenges interfering with immune maturation in early life. Understanding the mechanisms behind this immune dysfunction could inform prevention, detection and treatment of HL and other immune diseases.

Falls in the elderly were predicted opportunistically using a decision tree and systematically using a database-driven screening tool.

OBJECTIVE: To identify risk factors for falls and generate two screening tools: an opportunistic tool for use in consultation to flag at risk patients and a systematic database screening tool for comprehensive falls assessment of the practice population. STUDY DESIGN AND SETTING: This multicenter cohort study was part of the quality improvement in chronic kidney disease trial. Routine data for participants aged 65 years and above were collected from 127 general practice (GP) databases across the UK, including sociodemographic, physical, diagnostic, pharmaceutical, lifestyle factors, and records of falls or fractures over 5 years. Multilevel logistic regression analyses were performed to identify predictors. The strongest predictors were used to generate a decision tree and risk score. RESULTS: Of the 135,433 individuals included, 10,766 (8%) experienced a fall or fracture during follow-up. Age, female sex, previous fall, nocturia, anti-depressant use, and urinary incontinence were the strongest predictors from our risk profile (area under the receiver operating characteristics curve = 0.72). Medication for hypertension did not increase the falls risk. Females aged over 75 years and subjects with a previous fall were the highest risk groups from the decision tree. The risk profile was converted into a risk score (range -7 to 56). Using a cut-off of ≥9, sensitivity was 68%, and specificity was 60%. CONCLUSION: Our study developed opportunistic and systematic tools to predict falls without additional mobility assessments.

Serum phosphate as a risk factor for cardiovascular events in people with and without chronic kidney disease: a large community based cohort study.

BACKGROUND: Serum phosphate is a known risk factor for cardiovascular events and mortality in people with chronic kidney disease (CKD), however data on the association of these outcomes with serum phosphate in the general population are scarce. We investigate this relationship in people with and without CKD in a large community-based population. METHODS: Three groups from an adult cohort of the Quality Improvement in Chronic Kidney Disease (QICKD) cluster randomised trial (ISRCTN56023731) were followed over a period of 2.5 years: people with normal renal function (N = 24,184), people with CKD stages 1-2 (N = 20,356), and people with CKD stages 3-5 (N = 13,292). We used a multilevel logistic regression model to determine the association between serum phosphate, in these groups, and a composite outcome of all-cause mortality, cardiovascular events, and advanced coronary artery disease. We adjusted for known cardiovascular risk factors. FINDINGS: Higher phosphate levels were found to correlate with increased cardiovascular risk. In people with normal renal function and CKD stages 1-2, Phosphate levels between 1.25 and 1.50 mmol/l were associated with increased cardiovascular events; odds ratio (OR) 1.36 (95% CI 1.06-1.74; p = 0.016) in people with normal renal function and OR 1.40 (95% CI 1.09-1.81; p = 0.010) in people with CKD stages 1-2. Hypophosphatemia (<0.75 mmol/l) was associated with fewer cardiovascular events in people with normal renal function; OR 0.59 (95% CI 0.36-0.97; p = 0.049). In people with CKD stages 3-5, hyperphosphatemia (>1.50 mmol/l) was associated with increased cardiovascular risk; OR 2.34 (95% CI 1.64-3.32; p<0.001). Other phosphate ranges were not found to have a significant impact on cardiovascular events in people with CKD stages 3-5. CONCLUSIONS: Serum phosphate is associated with cardiovascular events in people with and without CKD. Further research is required to determine the mechanisms underlying these associations.

Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations.

OBJECTIVE: Neonatal diabetes can result from mutations in the Kir6.2 or sulfonylurea receptor 1 (SUR1) subunits of the ATP-sensitive K(+) channel. Transfer from insulin to oral sulfonylureas in patients with neonatal diabetes due to Kir6.2 mutations is well described, but less is known about changing therapy in patients with SUR1 mutations. We aimed to describe the response to sulfonylurea therapy in patients with SUR1 mutations and to compare it with Kir6.2 mutations. RESEARCH DESIGN AND METHODS: We followed 27 patients with SUR1 mutations for at least 2 months after attempted transfer to sulfonylureas. Information was collected on clinical features, treatment before and after transfer, and the transfer protocol used. We compared successful and unsuccessful transfer patients, glycemic control before and after transfer, and treatment requirements in patients with SUR1 and Kir6.2 mutations. RESULTS: Twenty-three patients (85%) successfully transferred onto sulfonylureas without significant side effects or increased hypoglycemia and did not need insulin injections. In these patients, median A1C fell from 7.2% (interquartile range 6.6-8.2%) on insulin to 5.5% (5.3-6.2%) on sulfonylureas (P = 0.01). When compared with Kir6.2 patients, SUR1 patients needed lower doses of both insulin before transfer (0.4 vs. 0.7 units x kg(-1) x day(-1); P = 0.002) and sulfonylureas after transfer (0.26 vs. 0.45 mg x kg(-1) x day(-1); P = 0.005). CONCLUSIONS: Oral sulfonylurea therapy is safe and effective in the short term in most patients with diabetes due to SUR1 mutations and may successfully replace treatment with insulin injections. A different treatment protocol needs to be developed for this group because they require lower doses of sulfonylureas than required by Kir6.2 patients.